This funding opportunity announcement is designed to support biomedical knowledgebases. Biomedical knowledgebases under this announcement should have the primary function to extract, accumulate, organize, annotate, and link growing bodies of information related to core datasets. Support for data curation should include efficient and effective methods of curation that scale to the needs of community and include semi-automated methods. Support for software and tool development must be limited to that which provides essential functions or significantly increases the efficiency of operation of the knowledgebase. Applications that have a significant focus on software and tool development are not appropriate for this activity.

This FOA invites applications for Centers for Collaborative Research in Fragile X and FMR1-Associated Conditions (hereafter termed "Fragile X Centers"). Successful Centers will be composed of multidisciplinary teams of investigators collaborating to address specific research priorities identified in the Strategic Plan.

This Funding Opportunity Announcement (FOA) encourages research grant applications directed toward developing next-generation human cell-derived microphysiological systems (MPS) and related assays that replicate complex nervous system architectures and physiology with improved fidelity over current capabilities. Supported projects will be expected to enable future studies of complex nervous system development, function and aging in healthy and disease states.

Despite established associations between white matter lesions and cognitive impairment including dementia, the volume, anatomical location, and other key cellular and molecular characteristics of white matter lesions that are both necessary and sufficient are unknown, as are the comorbid clinical factors that may modify (including protect from) these effects. Therefore, this initiative will support one large prospective clinical research study in the U.S. studying individuals with white matter lesions at risk for cognitive decline to determine the magnitude and anatomical locations that are both necessary and sufficient to cause cognitive impairment and dementia. The study will include health disparities populations, and will examine additional clinical factors and comorbidities that may be effect modifiers of the relationship between white matter lesions and cognitive impairment, including dementia. Clinical trial-ready VCID biomarkers should be utilized, further developed, and/or subject to implementation research in this study. Secondary goals include: identifying clinical and mechanistic targets for future VCID interventional trials; determining interrelationships (cross-sectional and longitudinal) among white matter lesions, cerebro- and cardio-vascular disease and risk factors including dementia-relevant genes. Applicants are encouraged, when scientifically advantageous, to utilize existing resources for VCID and stroke research, e.g. MarkVCID, StrokeNet, Alzheimers Centers, and large NIH funded prospective cohort studies (e.g. Framingham, ARIC, CHS, NOMAS, etc.) as well as other dementia resources.